Aspergillic acid as an antihypertensive agent

ABSTRACT

METHOD OF TREATING HYPERTENSION BY ADMINISTERING TO A HYPERTENSIVE PATIENT A THERAPWUTICALLY EFFECTIVE AMOUNT OF A COMPOUND OF THE FORMULA   O=N&lt;(=C(-OH)-(R3-)C=X(-R4)-(R1-)C=C(-R2)-) OR   HO-N&lt;(-C(=O)-(R3-)C=X(-R4)-(R1-)C=C(-R2)-)   WHEREIN X IIS C OR N; AND R1, R2, R3 AND R4 EACH ARE HYDROGEN, ALKYL, CYCLOALKYL OR ARYL, WITH THE LIMITATION THAT R4 IS PRESENT ONLY WHEN X IS C.

United States Patent O 3,720,768 ASPERGILLIC ACID AS AN ANTI- HYPERTENSIVE AGENT Peter Hadley Jones, Lake Forest, and Yvonne Connolly Martin, Waukegan, 111., assignors to Abbott Laboratories, North Chicago, Ill. No Drawing. Filed Nov. 22, 1971, Ser. No. 201,176 Int. Cl. A61k 27/00 U.S. Cl. 424-250 1 Claim ABSTRACT OF THE DISCLOSURE Method of treating hypertension by administering to a hypertensive patient a therapeutically effective amount of a compound of the Formula wherein X is C or N; and R R R and R each are hydrogen, alkyl, cycloalkyl or aryl, with the limitation that R; is present only when X is C.

DETAILED DESCRIPTION OF THE INVENTION wherein X is C or N; and R R R and R each are hydrogen, alkyl, cycloalkyl or aryl with the limitation that R; is present only when X is C.

Representative compounds which are represented by the above formula include:

3-n-pentyl-1-hydroxy-2-( 1H) -pyrazinone 5 -n-pentyll-hydroxy-2-( 1H) -pyrazinone 6-n-pentyl-1-hydroxy-2-( 1H) -pyrazinone 3,6-diethyl-l-hydroxy-2- 1H) -pyrazinone 3-ethyl-6-n-butyl-2- 1H) -pyrazinone 5-ethyl-6-propyl-2- 1H) -pyrazinone 5-ethyl-6-isopropyl-2-( 1H) -pyrazinone 3,5 ,6-triethy1-2- 1H) -pyrazinone 3,5 -diethyl-6-propy1-2- 1H) -pyrazinone 5-phenyl-6methyl-2-( 1H)-pyrazinone 5-cyclohexyl-3-methyl-2- 1H -pyrazinone 5-n-butyl-1-hydroxy-2-( 1H)-pyridone 3-n-butyll-hydroxy-2-( 1H -pyridone 4-n-butyl-1-hydroxy-2-( 1H) -pyridone 6-n-butyl-1-hydroxy-2-( 1H)-pyridone 6-ethyl3-propyl-2-( 1H)-pyridone 6-ethyl-3-isopropyl-2- 1H -pyridone 4-isobutyl-1-hydroxy-2- 1H) -pyridone 3-isobutyl-6sec-butyl-2- 1H -pyridone 5-cyclohexyl-3-methyl-2-( 1H -pyridone 4-cyclopentyl- 6-ethyl-2-( 1H) -pyridone 5 -phenyl-3-ethyl-2-( 1H -pyridone 3-phenyl-6-ethyl-2- 1H) -pyridone The compounds useful in the practice of this invention can be prepared by methods well known in the art. See, for example, Dunn et al., Pyrazine Derivatives XI Synthesis of Cyclic Hydroxarnic Acids Related to Aspergillic Acid J. Chem. Soc., 1949, 2707-l2; U.S. 2,666,054; France 2,022,146 and GB. 1,238,106.

The antihypertensive activity of the compounds useful in the practice of this invention was first established in the spontaneously hypertensive rate using standard procedures. The compounds are effective as antihypertensive agents at dosages of from 60 to 200 mg./kg. of body Weight daily.

In the practice of this invention, the compounds are administered to hypertensive patients, preferably by the oral route, in divided dosages, i.e., three to four times daily. They may also be co-administered with, for example, diuretics or tranquilizers in treating hypertension.

While the compounds can be administered alone, that is, as the sole component of a filled capsule, it is preferred to formulate the compound in various dosage forms for oral or parenteral administration such as tablets, syrups, sterile aqueous or non-aqueous suspension and the like. The oral dosage forms are prepared by methods well known in the art (as are the parenteral) and generally in clude a pharmaceutically acceptable carrier or diluent such as lactose, starch or sucrose along with lubricating agents such as magnesium stearate and flavoring and sweetening agents and the like.

We claim:

1. A method of reducing blood pressure in hypertensive patients which comprises administering to said patients an antihypertensively effective amount of aspergillic acid.

References Cited UNITED STATES PATENTS 2,666,054 1/1954 Safir 260-250 FOREIGN PATENTS 2,022,146 7/ 1970 France. 1,238,106 7/1971 Great Britain.

OTHER REFERENCES Dunn et al. J. Chem. Soc. (1949) pp. 2707-2712.

JEROME D. GOLDBERG, Primary Examiner A. J. ROBINSON, Assistant Examiner U.S. C1. X.R. 424-263 

